Intercellular Adhesion Molecule-2 (ICAM-2) is a 60 kDa surface glycoprotein that promotes adhesion between immune cells and the vascular endothelium. ICAM-2 is a member of the Ig-superfamily with two immunoglobulin-like extracellular domains. ICAM-2 is much more closely related to the two N-terminal domains of ICAM-1 (34% identity) than either ICAM-1 or ICAM-2 is to other members of the Ig-superfamily, demonstrating the existence of a subfamily of Ig-like ligands that bind the same integrin receptor. ICAM-2 is broadly distributed on hematopoietic cells. On resting lymphocytes, the ICAM-2 expression is several-fold higher than that seen with ICAM-1, while monocytes express equivalent levels of ICAM-1 and ICAM-2. In contrast to ICAM-1, neutrophils stain negative for ICAM-2. Just little or no ICAM-2 staining can be demonstrated on other cell lines, the sole exception being (i) resting vascular endothelial cells, which possess high levels of ICAM-2, and (ii) small clusters of cells in lymphoid tissue germinal centres. ICAM-2 expression is unaffected by a variety of inflammatory cytokines, while ICAM-1 is upregulated upon stimulation. This points toward the importance of ICAM-2 in the unstimulated resting state, before ICAM-1 expression is increased. The integrin LFA-1 is the receptor for ICAM-2 and ICAM-1 as well. The functional characteristics of ICAM-2 as LFA-1 ligand can be summarized as follows: ICAM-2 dominates over ICAM-1 on resting endothelial cells and seems to be involved in the recirculation of LFA-1 positive lymphocytes, e.g. facilitating T-memory cell recirculation. As resting T-cells express little or no ICAM-1, ICAM-2 may also be important in initial T-cell adhesion with antigen-presenting cells that bear LFA-1. Also the lysis of certain target cells appears to occur in an ICAM-1 independent manner, possibly regulated by ICAM-2.